Inherently chiral calix[4]arenes via oxazoline directed ortholithiation: synthesis and probe of chiral space

Abstract

SummaryThe diastereoselective oxazoline-directed lithiation of calix[4]arenes is reported with diastereoselective ratios of greater than 100:1 in some instances. Notably, it has been found that the opposite diastereomer can be accessed via this approach merely through the choice of an alkyllithium reagent. The inherently chiral oxazoline calix[4]arenes have also been preliminarily examined as ligands in the palladium-catalyzed Tsuji–Trost allylation reaction, returning results comparable to their planar chiral ferrocene counterparts pointing towards future application of these types of compounds.

Inherently Chiral Calix[4]arenes: A Chiral Sulfoxide as an Ortholithiation Director

“…We, like some others, [6] have focused our approach towards the meta-substitution pattern. [5] We have also reported that a [4]arene. In this regard, we have already demonstrated that chiral oxazolines can be used to stereoselectively direct ortholithiation of calix [4]arenes and give inherently chiral calixarenes in high diastereomeric excess.…”

“…Interestingly, the 1 H NMR spectrum of calix [4]arene substituted with the chiral sulfoxide 2 revealed the incorporated tert-butyl group to resonate at δ = 0.61 ppm, which was significantly upfield shifted compared to δ = 1.16 ppm for the analogous p-methoxyaryl sulfoxide. [5] We then examined diethyl ether as a solvent, but this resulted in no conversion after lithiation for eight hours at -78°C. This result looked promising regarding the ability of the sulfoxide to asymmetrically direct ortholithiation, since a preferred conformation was expected to lead to a high degree of diastereoselectivity.…”

“…Many intriguing inherently chiral motifs have been reported in the literature, but often these compounds are synthesized in racemic form and resolved through physical means. Only few reports have emerged in this regard, [5] which points to the significant challenge in achieving a synthetic protocol that is stereoselective. Only few reports have emerged in this regard, [5] which points to the significant challenge in achieving a synthetic protocol that is stereoselective.…”

“…For example, decorating the upper or lower rim, or the meta positions of a calix [4]arene as shown in Figure 1 would give inherently chiral calix- [4]arenes. [5] Our rationale has been that calixarenes could be employed in asymmetric catalysis as chiral ligands, and the meta substitution has close resemblance to the planar chirality of ferrocenes. We, like some others, [6] have focused our approach towards the meta-substitution pattern.…”

“…[5] Our rationale has been that calixarenes could be employed in asymmetric catalysis as chiral ligands, and the meta substitution has close resemblance to the planar chirality of ferrocenes. We demonstrate good diastereoselectivity (dr = 95: 5) in the reaction, and also provide proof of the major diastereomer through single-crystal X-ray diffraction. [5] We have also reported that a [4]arene.…”